Single position robot-assisted pedicle screw placement with S2-alar-iliac fixation in lateral decubitus: cadaveric feasibility study and early clinical experience.

OBJECTIVES: Single position lateral fusion with robotic assistance eliminates the need for surgical staging while harnessing the precision of robotic adjuncts. We expand on this technique by demonstrating the technical feasibility of placing bilateral pedicle screws with S2-alar-iliac (S2AI) fixation while in the lateral position. METHODS: A cadaveric study was performed using 12 human specimens. A retrospective clinical series was also performed for patients who had undergone robot-assisted placement of S2AI screws in lateral decubitus between June 2020 and June 2022. Case demographics, implant placement time, implant size, screw accuracy, and complications were recorded. Early postoperative radiographic outcomes were reported. RESULTS: In the cadaveric series, a total of 126 screws were placed with robotic assistance in 12 cadavers of which 24 screws were S2AI. There were four breaches from pedicle screws and none with S2AI screws for an overall accuracy rate of 96.8%. In the clinical series, four patients (all male, mean age 65.8 years) underwent single position lateral surgery with S2AI distal fixation. Mean BMI was 33.6 and mean follow-up was 20.5 months. Mean radiographic improvements were lumbar lordosis 12.3 ± 4.7°, sagittal vertical axis 1.5 ± 2.1 cm, pelvic tilt 8.5 ± 10.0°, and pelvic incidence-lumbar lordosis mismatch 12.3 ± 4.7°. A total of 42 screws were placed of which eight screws were S2AI. There were two breaches from pedicle screws and none from S2AI screws for an overall accuracy rate of 95.2%. No repositioning or salvage techniques were required for the S2AI screws. CONCLUSIONS: We demonstrate here the technical feasibility of single position robot-assisted placement of S2-alar-iliac screws in the lateral decubitus position for single position surgery.

Massive Acute Spinal Subdural Hematoma Causing Sudden Onset Paraplegia in a Patient on Anticoagulation.

Spinal subdural hematoma (SSDH) is a rare but known entity that can cause severe and irreversible motor, sensory, and autonomic dysfunction if not decompressed in a timely manner. We present here a 74-year-old female on anticoagulation who developed sudden onset back pain with rapidly progressive paraplegia. On neurologic exam, she was completely flaccid in the bilateral lower extremities with absent sensation from the umbilicus down. Imaging demonstrated a massive extra-axial spinal hematoma from T12 to S1 that initially was believed to be epidural in origin. She was taken emergently to the operating room for a T11-L5 decompressive laminectomy, and dural opening demonstrated a thick subdural clot encasing the conus and cauda equina confirming the subdural pathology. Despite decompression and partial evacuation of the subdural hematoma, she did not recover neurologic function.

Management of Giant Sacral Pseudomeningocele in Revision Spine Surgery.

BACKGROUND: Giant pseudomeningoceles are an uncommon complication of spine surgery. Surgical management and extirpation can be difficult, and guidelines remain unclear. METHODS: Here, we present a 56-year-old female patient with a history of grade III L5-S1 spondylolisthesis who was treated with 2 prior spine surgeries. The patient was treated with bone grafting for pseudarthrosis and instrumentation from L4 to ilium. After unsuccessful intraoperative and postoperative cerebrospinal fluid drainage and dural repair, the patient presented to the emergency room with debilitating positional headaches. RESULTS: The patient underwent dural repair with bovine pericardial patch inlay sutured with 7-0 prolene, blood patch, and a dural sealant. Plastic surgery performed a layered closure, using acellular dermal matrix over the dural closure. The bilateral paraspinal flaps were advanced medially to cover the entirety of the acellular dermal matrix, and the fasciocutaneous flaps were then advanced to the midline for a watertight closure. At 3-month follow-up, the patient was headache free and had returned to her activities of daily living. CONCLUSIONS: We conclude that early consultation with plastic surgery can be greatly beneficial to effectively extirpate dead space and resolve giant sacral pseudomeningoceles, especially if there is concern of persistent cerebrospinal fluid leakage due to relatively immobile avascular soft tissue as a result of prior revision surgery.

Decompression Surgery versus Interspinous Devices for Lumbar Spinal Stenosis: A Systematic Review of the Literature.

In this retrospective review study, the authors systematically reviewed the literature to elucidate the efficacy and complications associated with decompression and interspinous devices (ISDs) used in surgeries for lumbar spinal stenosis (LSS). LSS is a debilitating condition that affects the lumbar spinal cord and spinal nerve roots. However, a comprehensive report on the relative efficacy and complication rate of ISDs as they compare to traditional decompression procedures is currently lacking. The PubMed database was queried to identify clinical studies that exclusively investigated decompression, those that exclusively investigated ISDs, and those that compared decompression with ISDs. Only prospective cohort studies, case series, and randomized controlled trials that evaluated outcomes using the Visual Analog Scale (VAS), Oswestry Disability Index, or Japanese Orthopedic Association scores were included. A random-effects model was established to assess the difference between preoperative and the 1-2-year postoperative VAS scores between ISD surgery and lumbar decompression. This study included 40 papers that matched our criteria. Twenty-five decompression-exclusive clinical trials with 3,386 patients and a mean age of 68.7 years (range, 31-88 years) reported a 2.2% incidence rate of dural tears and a 2.6% incidence rate of postoperative infections. Eight ISD-exclusive clinical trials with 1,496 patients and a mean age of 65.1 (range, 19-89 years) reported a 5.3% incidence rate of postoperative leg pain and a 3.7% incidence rate of spinous process fractures. Seven studies that compared ISDs and decompression in 624 patients found a reoperation rate of 8.3% in ISD patients vs. 3.9% in decompression patients; they also reported dural tears in 0.32% of ISD patients vs. 5.2% in decompression patients. A meta-analysis of the randomized controlled trials found that the differences in preoperative and postoperative VAS scores between the two groups were not significant. Both decompression and ISD interventions are unique surgical interventions with different therapeutic efficacies and complications. The collected studies do not consistently demonstrate superiority of either procedure over the other but understanding the differences between the two techniques can help tailor treatment regimens for patients with LSS.

Use of a Reverse Bohlman Technique for Low-Grade Spondylolisthesis.

BACKGROUND: Treatment of spondylolisthesis can be difficult with regard to patients with high sacral slopes that may prohibit placement of interbody grafts for fusions across that segment. Here, we describe placement of a reverse Bohlman technique from an anterior approach to obtain fusion across a low-grade spondylolisthesis with a high sacral slope to obtain anterior fusion. METHODS: A chart review was conducted on this single patient regarding his clinical course and outcome. RESULTS: A 54-year-old male presented with low-back pain associated with bilateral leg pain dating back several years. Plain films demonstrated a Grade II isthmic spondylolisthesis at L5-S1 with spinopelvic measurements of 73° sacral slope, 82° lumbar lordosis, 12° pelvic tilt, and 94° pelvic incidence. Magnetic resonance imaging showed bilateral L5 pars defects with diffuse degenerative disease from L4 through S1 and significant ligamentous and facet hypertrophy. He underwent an L4-5 anterior lumbar interbody fusion and an L5-S1 reverse Bohlman placement of a transvertebral transsacral titanium mesh cage. This was supplemented with a posterior decompression and instrumentation from L4-ilium. He had resolution of his radiculopathy and has maintained a good clinical outcome at 3 years follow up. CONCLUSIONS: We present here a patient with low-grade spondylolisthesis and a steep sacral slope who underwent a successful reverse Bohlman approach with long-term follow up. This report highlights the potential utility of this method as a viable alternative for patients with low-grade spondylolisthesis. LEVEL OF EVIDENCE: IV. CLINICAL RELEVANCE: Technical description of surgical technique.

Feasibility of a Fourth Ventriculopleural Shunt for Diversion of an Isolated Fourth Ventricle: A Technical Note.

Isolated fourth ventricle syndrome is an uncommon entity due to obstruction of both inlet and outflow foramina. The resulting mass effect from the progressively expanding fourth ventricle may cause symptoms from both cerebellar and brainstem compression. Although a variety of treatment modalities have been advocated for this condition, an in-depth description of placement of a fourth ventriculopleural (VPL) shunt from a single-stage prone approach has not yet been published in the literature. We describe here a case of successful placement of a fourth VPL shunt in a 22-year-old female with a history of a prior posterior fossa pilocytic astrocytoma resection who presented with symptomatic isolated fourth ventricular hydrocephalus.

Genetic Risk for Subsequent Neoplasms Among Long-Term Survivors of Childhood Cancer.

Purpose Childhood cancer survivors are at increased risk of subsequent neoplasms (SNs), but the germline genetic contribution is largely unknown. We assessed the contribution of pathogenic/likely pathogenic (P/LP) mutations in cancer predisposition genes to their SN risk. Patients and Methods Whole-genome sequencing (30-fold) was performed on samples from childhood cancer survivors who were ≥ 5 years since initial cancer diagnosis and participants in the St Jude Lifetime Cohort Study, a retrospective hospital-based study with prospective clinical follow-up. Germline mutations in 60 genes known to be associated with autosomal dominant cancer predisposition syndromes with moderate to high penetrance were classified by their pathogenicity according to the American College of Medical Genetics and Genomics guidelines. Relative rates (RRs) and 95% CIs of SN occurrence by mutation status were estimated using multivariable piecewise exponential regression stratified by radiation exposure. Results Participants were 3,006 survivors (53% male; median age, 35.8 years [range, 7.1 to 69.8 years]; 56% received radiotherapy), 1,120 SNs were diagnosed among 439 survivors (14.6%), and 175 P/LP mutations were identified in 5.8% (95% CI, 5.0% to 6.7%) of survivors. Mutations were associated with significantly increased rates of breast cancer (RR, 13.9; 95% CI, 6.0 to 32.2) and sarcoma (RR, 10.6; 95% CI, 4.3 to 26.3) among irradiated survivors and with increased rates of developing any SN (RR, 4.7; 95% CI, 2.4 to 9.3), breast cancer (RR, 7.7; 95% CI, 2.4 to 24.4), nonmelanoma skin cancer (RR, 11.0; 95% CI, 2.9 to 41.4), and two or more histologically distinct SNs (RR, 18.6; 95% CI, 3.5 to 99.3) among nonirradiated survivors. Conclusion The findings support referral of all survivors for genetic counseling for potential clinical genetic testing, which should be prioritized for nonirradiated survivors with any SN and for those with breast cancer or sarcoma in the field of prior irradiation.

Racial disparities in BRCA testing and cancer risk management across a population-based sample of young breast cancer survivors.

BACKGROUND: Breast cancer (BC) disparities may widen with genomic advances. The authors compared non-Hispanic white (NHW), black, and Hispanic BC survivors for 1) cancer risk-management practices among BRCA carriers and 2) provider discussion and receipt of genetic testing. METHODS: A population-based sample of NHW, black, and Hispanic women who had been diagnosed with invasive BC at age 50 years or younger from 2009 to 2012 were recruited through the state cancer registry. Multiple logistic regression was used to compare cancer risk-management practices in BRCA carriers and associations of demographic and clinical variables with provider discussion and receipt of testing. RESULTS: Of 1622 participants, 159 of 440 (36.1%) black women, 579 of 897 (64.5%) NHW women, 58 of 117 (49.6%) Spanish-speaking Hispanic women, and 116 of 168 (69%) English-speaking Hispanic women underwent BRCA testing, of whom 90 had a pathogenic BRCA mutation identified. Among BRCA carriers, the rates of risk-reducing mastectomy and risk-reducing salpingo-oophorectomy were significantly lower among black women compared with Hispanic and NHW women after controlling for clinical and demographic variables (P = .025 and P = .008, respectively). Compared with NHW women, discussion of genetic testing with a provider was 16 times less likely among black women (P < .0001) and nearly 2 times less likely among Spanish-speaking Hispanic women (P = .04) after controlling for clinical and sociodemographic factors. CONCLUSIONS: The current results suggest that the rates of risk-reducing salpingo-oophorectomy are lower among black BRCA carriers compared with their Hispanic and NHW counterparts, which is concerning because benefits from genetic testing arise from cancer risk-management practice options. Furthermore, lower BRCA testing rates among blacks may partially be because of a lower likelihood of provider discussion. Future studies are needed to improve cancer risk identification and management practices across all populations to prevent the widening of disparities. Cancer 2017;123:2497-05. © 2017 American Cancer Society.

Hereditary Cancer: Example of a Public Health Approach to Ensure Population Health Benefits of Genetic Medicine.

This article introduces the identification, prevention, and treatment of hereditary cancer as an important public health concern. Hereditary cancer research and educational outreach activities are used to illustrate how public health functions can help to achieve health benefits of genetic and genomic medicine. First, we evaluate genetic service delivery through triangulating patient and provider survey results which reveal variability among providers in hereditary cancer knowledge and genetic service provision. Second, we describe efforts we have made to assure competency among healthcare providers and to inform, educate and empower patients with regard to the rapidly evolving field of genomics and hereditary cancer. Lastly, key policy-issues raised by our experiences are discussed in the context of how they may help us to more effectively translate future genomic technologies into practice in order to attain population health benefits from genetic and genomic medicine.

Comparing the Maryland Comprehensive Cancer Control Plan With Federal Cancer Prevention and Control Recommendations.

INTRODUCTION: Since the introduction of the Affordable Care Act (ACA) in 2012, 11 million more Americans now have access to preventive services via health care coverage. Several prevention-related recommendations issued by the US Preventive Services Task Force (USPSTF), Centers for Disease Control and Prevention (CDC), and Advisory Committee on Immunization Practices (ACIP) are covered under the ACA. State cancer plans often provide prevention strategies, but whether these strategies correspond to federal evidence-based recommendations is unclear. The objective of this article is to assess whether federal evidence-based recommendations, including those covered under the ACA, are included in the Maryland Comprehensive Cancer Control Plan (MCCCP). METHODS: A total of 19 federal recommendations pertaining to cancer prevention and control were identified. Inclusion of federal cancer-related recommendations by USPSTF, CDC, and ACIP in the MCCCP's goals, objectives, and strategies was examined. RESULTS: Nine of the federal recommendations were issued after the MCCCP's publication. MCCCP recommendations corresponded completely with 4 federal recommendations and corresponded only partially with 3. Reasons for partial correspondence included specification of less restrictive at-risk populations or different intervention implementers. Three federal recommendations were not mentioned in the MCCCP's goals, objectives, and strategies. CONCLUSION: Many cancer-related federal recommendations were released after the MCCCP's publication and therefore do not appear in the most current version. We recommend that the results of this analysis be considered in the update of the MCCCP. Our findings underscore the need for a periodic scan for changes to federal recommendations and for adjusting state policies and programs to correspond with federal recommendations, as appropriate for Marylanders.

Normal CFTR inhibits epidermal growth factor receptor-dependent pro-inflammatory chemokine production in human airway epithelial cells.

Mutations in cystic fibrosis transmembrane conductance regulator (CFTR) protein cause cystic fibrosis, a disease characterized by exaggerated airway epithelial production of the neutrophil chemokine interleukin (IL)-8, which results in exuberant neutrophilic inflammation. Because activation of an epidermal growth factor receptor (EGFR) signaling cascade induces airway epithelial IL-8 production, we hypothesized that normal CFTR suppresses EGFR-dependent IL-8 production and that loss of CFTR at the surface exaggerates IL-8 production via activation of a pro-inflammatory EGFR cascade. We examined this hypothesis in human airway epithelial (NCI-H292) cells and in normal human bronchial epithelial (NHBE) cells containing normal CFTR treated with a CFTR-selective inhibitor (CFTR-172), and in human airway epithelial (IB3) cells containing mutant CFTR versus isogenic (C38) cells containing wild-type CFTR. In NCI-H292 cells, CFTR-172 induced IL-8 production EGFR-dependently. Pretreatment with an EGFR neutralizing antibody or the metalloprotease TACE inhibitor TAPI-1, or TACE siRNA knockdown prevented CFTR-172-induced EGFR phosphorylation (EGFR-P) and IL-8 production, implicating TACE-dependent EGFR pro-ligand cleavage in these responses. Pretreatment with neutralizing antibodies to IL-1R or to IL-1alpha, but not to IL-1beta, markedly suppressed CFTR-172-induced EGFR-P and IL-8 production, suggesting that binding of IL-1alpha to IL-1R stimulates a TACE-EGFR-IL-8 cascade. Similarly, in NHBE cells, CFTR-172 increased IL-8 production EGFR-, TACE-, and IL-1alpha/IL-1R-dependently. In IB3 cells, constitutive IL-8 production was markedly increased compared to C38 cells. EGFR-P was increased in IB3 cells compared to C38 cells, and exaggerated IL-8 production in the IB3 cells was EGFR-dependent. Activation of TACE and binding of IL-1alpha to IL-1R contributed to EGFR-P and IL-8 production in IB3 cells but not in C38 cells. Thus, we conclude that normal CFTR suppresses airway epithelial IL-8 production that occurs via a stimulatory EGFR cascade, and that loss of normal CFTR activity exaggerates IL-8 production via activation of a pro-inflammatory EGFR cascade.

Educational needs and preferred methods of learning among Florida practitioners who order genetic testing for hereditary breast and ovarian cancer.

With the expansion of genetic testing options due to tremendous advances in sequencing technologies, testing will increasingly be offered by a variety of healthcare providers in diverse settings, as has been observed with BRCA1 and BRCA2 (BRCA) gene testing over the last decade. In an effort to assess the educational needs and preferences of healthcare providers primarily in a community-based setting, we mailed a survey to healthcare providers across Florida who order BRCA testing. Within the packet, a supplemental card was included to give participants the opportunity to request free clinical educational resources from the investigative team. Of 81 eligible providers who completed the survey, most were physicians or nurse practitioners; and over 90 % worked in a community or private practice setting. Respondents provided BRCA testing services for a median of 5 years, but the majority (56 %) reported no formal training in clinical cancer genetics. Most respondents (95 %) expressed interest in formal training opportunities, with 3-day in-person weekend training representing the most highly preferred format. The most widely selected facilitators to participation were minimal requirement to take time off work and continuing education credits. Overall, 64 % of respondents requested free clinical educational resources. Preferences for informal education included written materials and in-person presentations; whereas accessing a DVD or website were less popular. Findings from our study highlight both the need for and interest in ongoing educational opportunities and resources among community providers who order BRCA testing. These results can be used to enhance participation of community-based providers in educational training programs by targeting educational resources to the most preferred format.

A statewide survey of practitioners to assess knowledge and clinical practices regarding hereditary breast and ovarian cancer.

PURPOSE: This study describes practitioner knowledge and practices related to BRCA testing and management and explores how training may contribute to practice patterns. METHODS: A survey was mailed to all BRCA testing providers in Florida listed in a publicly available directory. Descriptive statistics characterized participants and their responses. RESULTS: Of the 87 respondents, most were community-based physicians or nurse practitioners. Regarding BRCA mutations, the majority (96%) recognized paternal inheritance and 61% accurately estimated mutation prevalence. For a 35-year-old unaffected BRCA mutation carrier, the majority followed national management guidelines. However, 65% also recommended breast ultrasonography. Fewer than 40% recognized the need for comprehensive rearrangement testing when BRACAnalysis(®) was negative in a woman at 30% risk. Finally, fewer than 15% recognized appropriate testing for a BRCA variant of uncertain significance. Responses appeared to be positively impacted by presence and type of cancer genetics training. CONCLUSIONS: In our sample of providers who order BRCA testing, knowledge gaps in BRCA prevalence estimates and appropriate screening, testing, and results interpretation were identified. Our data suggest the need to increase regulation and oversight of genetic testing services at a policy level, and are consistent with case reports that reveal liability risks when genetic testing is conducted without adequate knowledge and training.

Epidermal growth factor receptor reactivation induced by E-prostanoid-3 receptor- and tumor necrosis factor-alpha-converting enzyme-dependent feedback exaggerates interleukin-8 production in airway cancer (NCI-H292) cells.

Airway epithelial cancer cells produce increased amounts of the chemokine interleukin-8 (IL-8), inducing pro-tumor responses. Multiple stimuli induce airway epithelial IL-8 production epidermal growth factor receptor (EGFR) dependently, but the mechanisms that exaggerate IL-8 production in airway cancers remain unknown. Here we show that direct activation of EGFR (EGFR-P) by its ligand transforming growth factor (TGF)-alpha induces a second EGFR-P in human airway (NCI-H292) cancer cells but not in normal human bronchial epithelial (NHBE) cells, exaggerating IL-8 production in these cancer cells. The second EGFR-P in NCI-H292 cells was caused by metalloprotease TNF-alpha-converting enzyme (TACE)-dependent cleavage of EGFR pro-ligands and was responsible for most of the total IL-8 induced by TGF-alpha. In NCI-H292 cells, TGF-alpha induced cyclooxygenase (COX)-2-dependent prostaglandin (PG)E2 production and release. PGE2 increased the second EGFR-P and IL-8 production via binding to its Gi-protein-coupled E-prostanoid (EP)3 receptor. In NHBE cells, TGF-alpha-induced EGFR-P did not lead to PGE2 production or to a second EGFR-P, and less IL-8 was produced. Thus, we conclude that a positive feedback pathway involving COX-2/PGE2/EP3 receptor-dependent EGFR reactivation exaggerates IL-8 production in NCI-H292 cancer cells but not in NHBE (normal) cells.

CCL20/CCR6 feedback exaggerates epidermal growth factor receptor-dependent MUC5AC mucin production in human airway epithelial (NCI-H292) cells.

Mucous hypersecretion is an important feature of obstructive airway diseases such as asthma, chronic obstructive pulmonary disease, and cystic fibrosis. Multiple stimuli induce mucin production via activation of an epidermal growth factor receptor (EGFR) cascade, but the mechanisms that exaggerate mucin production in obstructive airway diseases remain unknown. In this study, we show that binding of CCL20, a G protein-coupled receptor (GPCR) ligand that is upregulated in the airways of subjects with obstructive airway diseases, to its unique GPCR CCR6 induces MUC5AC mucin production in human airway epithelial (NCI-H292) cells via metalloprotease TNF-α-converting enzyme (TACE)-dependent EGFR activation. We also show that EGFR activation by its potent ligand TGF-α induces reactivation of EGFR via binding of endogenously produced CCL20 to its receptor CCR6 in NCI-H292 cells but not in normal human bronchial epithelial (NHBE) cells, exaggerating mucin production in the NCI-H292 cells. In NCI-H292 cells, TGF-α stimulation induced two phases of EGFR phosphorylation (EGFR-P). The second EGFR-P was TACE-dependent and was responsible for most of the total mucin induced by TGF-α. Binding of endogenously produced CCL20 to CCR6 increased the second EGFR-P and subsequent mucin production induced by TGF-α. In NHBE cells, TGF-α-induced EGFR activation did not lead to significant CCL20 production or to EGFR rephosphorylation, and less mucin was produced. We conclude that NCI-H292 cells but not NHBE cells produce CCL20 in response to EGFR activation, which leads to a second phase of EGFR-P and subsequent exaggerated mucin production. These findings have potentially important therapeutic implications in obstructive airway diseases.